Early Surgical Management of Thermal Airway Injury: A Case Series.

Inhalation injury is an independent risk factor in burn mortality, imparting a 20% increased risk of death. Yet there is little information on the natural history, functional outcome, or pathophysiology of thermal injury to the laryngotracheal complex, limiting treatment progress. This paper demonstrates a case series (n = 3) of significant thermal airway injuries. In all cases, the initial injury was far exceeded by the subsequent immune response and aggressive fibroinflammatory healing. Serial examination demonstrated progressive epithelial injury, mucosal inflammation, airway remodeling, and luminal compromise. Histologic findings in the first case demonstrate an early IL-17A response in the human airway following thermal injury. This is the first report implicating IL-17A in the airway mucosal immune response to thermal injury. Their second and third patients received Azithromycin targeting IL-17A and showed clinical responses. The third patient also presented with exposed tracheal cartilage and underwent mucosal reconstitution via split-thickness skin graft over an endoluminal stent in conjunction with tracheostomy. This was associated with rapid abatement of mucosal inflammation, resolution of granulation tissue, and return of laryngeal function. Patients who present with thermal inhalation injury should receive a thorough multidisciplinary airway evaluation, including early otolaryngologic evaluation. New early endoscopic approaches (scar lysis and mucosal reconstitution with autologous grafting over an endoluminal stent), when combined with targeted medical therapy aimed at components of mucosal airway inflammation (local corticosteroids and systemic Azithromycin targeting IL-17A), may have potential to limit chronic cicatricial complications.

The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome.

Burn injury causes major inflammatory activation and cytokine release, however, the temporal resolution of the acute and sub-acute inflammatory response has not yet been fully delineated. To this end, we have quantified 20 inflammatory mediators in plasma from 44 adult patients 0-21 days after burn injury and related the time course of these mediators to % total body surface area (TBSA) burned, clinical parameters, organ failure and outcome. Of the cytokines analyzed in these patients, interleukin 6 (IL-6), IL-8, IL-10 and monocyte chemoattractant protein 1 (MCP-1) correlated to the size of the injury at 24-48h after burn injury. In our study, the concentration of IL-10 had prognostic value in patients with burn injury both measured at admission and at 24-48h after injury. However, simple demographic data such as age, % burned TBSA, inhalation injury and their combination, the Baux score and modified Baux score, outperform most of the cytokines, with the exception of IL-8 and MCP-1 levels on admission, in predicting death.

Age-related immune responses after burn and inhalation injury are associated with altered clinical outcomes.

This prospective study aimed to address changes in inflammatory response between different aged populations of patients who sustained burn and inhalation injury. Plasma and bronchoalveolar lavage (BAL) samples were collected from 104 patients within 15h of their estimated time of burn injury. Clinical variables, laboratory parameters, and immune mediator profiles were examined in association with clinical outcomes. Older patients were at higher odds for death after burn injury (odds ratio (OR)=7.37 per 10years, p=0.004). In plasma collected within 15h after burn injury, significant increases in the concentrations of interleukin 1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), granulocyte colony-stimulating factor (G-CSF), interferon-gamma-induced protein 10 (IP-10) and monocyte chemoattractant protein 1 (MCP-1) (p<0.05 for all) were observed in the ≥65 group. In the BAL fluid, MCP-1 was increased three-fold in the ≥65 group. This study suggests that changes in certain immune mediators were present in the older cohort, in association with in-hospital mortality.

Inhalation injury severity and systemic immune perturbations in burned adults.

OBJECTIVE: We aimed to determine whether the severity of inhalation injury evokes an immune response measurable at the systemic level and to further characterize the balance of systemic pro- and anti-inflammation early after burn and inhalation injury. BACKGROUND: Previously, we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury and that those who die of injuries have a blunted pulmonary immune profile compared with survivors. METHODS: From August 2007 to June 2011, bronchoscopy was performed on 80 patients admitted to the burn intensive care unit when smoke inhalation was suspected. Of these, inhalation injury was graded into 1 of 5 categories (0, 1, 2, 3, and 4), with grade 0 being the absence of visible injury and grade 4 corresponding to massive injury. Plasma was collected at the time of bronchoscopy and analyzed for 28 immunomodulating proteins via multiplex bead array or enzyme-linked immunosorbent assay. RESULTS: The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % total body surface area (TBSA) burn. These included interleukin (IL)-1RA (P = 0.002), IL-6 (P = 0.002), IL-8 (P = 0.026), granulocyte colony-stimulating factor (P = 0.002), and monocyte chemotactic protein 1 (P = 0.007). Differences in plasma immune mediator concentrations in surviving and deceased patients were also identified. Briefly, plasma concentrations of IL-1RA, IL-6, IL-8, IL-15, eotaxin, and monocyte chemotactic protein 1 were higher in deceased patients than in survivors (P < 0.05 for all), whereas IL-4 and IL-7 were lower (P < 0.05). After adjusting for the effects of age, % TBSA burn, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (odds ratio, 3.12; 95% confidence interval, 1.03-9.44). Plasma IL-1RA also correlated with % TBSA burn, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score. CONCLUSIONS: The severity of smoke inhalation injury has systemically reaching effects, which argue in favor of treating inhalation injury in a graded manner. In addition, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA seemed to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in nonsurvivors.

[Methods of burn treatment. Part I: general aspects]. / Behandlungskonzepte bei Verbrennungen Teil I: Allgemeine Aspekte.

Burns and scalds are common injuries that present with a wide range of severity. Correct evaluation of a burn's depth and extent is essential for adequate treatment, not only initially but also for late results. The depth of a burn is classified as first-to-third degree, and its extent can be deducted from specific tables. As a generalised haemodynamic reaction, a capillary leak allows fluid and colloidal substances to leave the intravasal system. This can lead to hypovolemic shock. In the first 24 h, only cristalloid fluid according to Baxter's formula should be administered. Transfer to a burn centre is indicated in accordance with well-defined guidelines. Concomitant injuries, especially inhalation traumata, need to be diagnosed and treated early. By activation of the immune response, a sepsis-like immune response syndrome can occur,resulting in bacterial translocation and colonisation with high mortality rates.

Circulating endothelial cell levels correlate with proinflammatory cytokine increase in the acute phase of thermal injury.

Circulating endothelial cells (CECs) are increased in sickle cell disease, myocardial infarction, and acute lung injury. The purpose of this study was to determine whether CECs are a prognosticating marker for the development of pneumonia in burn patients with/without inhalation injury in addition to their relationship to proinflammatory cytokines. There were 24 patients: 6 with inhalation injury, 5 with burn only,and 13 with burn plus inhalation injury. CECs were measured by anchored cytometry (Clarient ChromaVision, San Juan Capistrano, CA). In addition, plasma levels of tumor necrosis factor-alpha, interferon-gamma, and interleukins (IL)-10, IL-6, IL-4, and IL-2 were compared with CEC levels. Patients with inhalation injury had a significant (P < .001) paucity of CECs compared with the thermally injured with inhalation. There was a statistically significant increase in inteferon-gamma, tumor necrosis factor-alpha, and IL-6, IL-4, and IL-2 compared with control patients (P < .01), with a concomitant increase in the number of CECs. The numbers of CEC levels did not prognosticate which patients would develop pneumonia. Burn patients with/without inhalation injury had concurrent increase in CECs and proinflammatory cytokines during the acute phase of injury.

Acute bronchial obstruction in sheep: histopathology and gland cytokine expression.

An ovine model of smoke inhalation and burn (S+B) injury models the pathophysiology of these injuries in humans. This study examines the degree of airway obstruction, associated histopathology, and bronchial gland cell expression of cytokines during the first 24 hours after S+B injury in sheep. Changes in the mean degree of obstruction were limited to the bronchial airways, showing significant increases in obstruction with time, P<.05. At 4 hours after injury, the obstructive material was predominantly mucus, with neutrophils clustered around and within gland acini. At 8 to 24 hours, bronchial obstruction was characterized by increased inflammatory cell accumulation. Immunohistochemical results showed that gland cells constitutively express and secrete interleukin (IL)-1beta, and that after injury there is an increase in the percentage of gland cells staining for IL-1alpha, IL-8, and tumor necrosis factor (TNF)-alpha, P<.05.

Trauma and thermal injury: comparison of hemostatic and cytokine changes in the acute phase of injury.

BACKGROUND: Initiated either by thermal injury or mechanical trauma, the systemic inflammatory response syndrome stimulates activation of coagulation and fibrinolysis, evolving into a subclinical disseminated intravascular coagulation. METHOD: Hemostatic parameters, interleukin-6, and endothelin plasma levels were compared in burn and trauma patients. Nineteen patients with major burn injury (> or = 40% total body surface area) were compared with 35 trauma patients with Injury Severity Scores > 25 on day 1 and days 5 to 8. RESULTS: Thrombin-antithrombin levels were significantly higher in trauma patients than in burn patients (p < 0.0001) on day 1, and endothelin was significantly higher on days 1 and 5 (p < 0.0001) in trauma patients than in burn patients. Interleukin-6 plasminogen activator inhibitor-1, and tissue plasminogen activator levels were elevated above normal limits on both days in both groups. CONCLUSION: There was a difference in the degree and level to which homeostasis was perturbed between the two groups. The mechanism of injury did not affect the initiation of subclinical disseminated intravascular coagulation and cytokine release, and the physiologic response remained the same.

[Serum IgG concentrations and antibody titer of burn patients after preventive intravenous IgG substitution with a Pseudomonas immunoglobulin]. / IgG-Serum-Konzentrationen und Antikörpertiter brandverletzter Patienten nach prophylaktischer intravenöser IgG-Substitution mit einem Pseudomonas-Immunglobulin.

In a randomized clinical trial 30 patients with burn injury received supportive therapy with a Pseudomonas hyperimmunoglobulin (Psomaglobin N). The control group received no additional therapy. The patients of both groups were between 15 and 60 years of age and had a full-thickness burn of 30-70% of the body surface area with inhalational trauma being optional. The whole trauma was classified and scored with the 'Abbreviated Burn Severity Index' (which allows another extra score point for inhalational trauma). Both groups underwent the same intensive care unit treatment with preference to early wound excision and wound grafting following functional aspects of reconstructive surgery. Bacteriological monitoring was performed on suspicion of wound infection and bacteremia by taking wound swabs and blood cultures. The supportive treatment group received a total of 250 mg/kg hyperimmunoglobulin on days 3, 5, 7, 10, and 13. Of 30 patients in the control group 16 had an additional inhalation trauma, and 8 of those (50%) died (only 1 of 14 patients without inhalation trauma died). In the group receiving supportive treatment, 23 out of 30 patients had an inhalation trauma, and 8 of those (35%) died (1 of 7 patients without inhalation trauma). In both groups with inhalation injury, the patients were at risk of developing bacteremia: 13 of 23 of the immunoglobulin-treated patients and 12 of 16 patients of the control group. Bacteremic controls died at a lower score than bacteremic immunoglobulin-treated patients (8.6 vs. 10.3 points).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoglobulin E pattern in cigarette smokers.

Serum IgE levels in healthy blood donors who had no history of atopy were measured by a paper-disc RIA and analyzed according to the donors' smoking habits. The IgE geometric mean for regular smokers was 41.7 IU/ml, which was significantly higher than that for nonsmokers (19.3 IU/ml) or rare smokers (22.7 IU/ml). Whereas 28% of smokers had IgE levels greater than 200 IU/ml, none of the rare smokers or nonsmokers did. IgE levels in smokers showed a moderate inverse correlation with the degree of smoking. The mean IgE level was 189.8 IU/ml in those who smoked 1-9 cigarettes/day but only 32.8 IU/ml in those who smoked 10-19 cigarettes per day and 11.1 IU/ml in those who smoked 20 or more cigarettes/day. The number of years a person smoked did not seem to significantly influence the IgE level. The mean IgE level in ex-smokers (50.5 IU/ml) was much lower than in current light smokers but was still higher than in nonsmokers. There was a moderate inverse correlation between IgE levels and duration of cessation of smoking. Our data suggest a characteristic pattern for the influence of cigarette smoking on serum IgE level, namely, a striking rise associated with light smoking and a remarkable drop in heavy smokers, and such changes seemed reversible after the habit was stopped. Smoking status, therefore, appears to be an important consideration in interpreting serum IgE levels and in revising the "norms" of IgE levels.